High Performance Liquid Chromatographic Method for the Determination of Diphenhydramine in Liquid and Solid Drug Dosage Forms and Its Application to Stability Testing

Abstract

A simple, precise, rugged, stability-indicating method for diphenhydramine in liquid and solid drug preparations based on reversed phase ion-pair HPLC is described. The eluent used with the C8-bonded phase column, was acetonitrile/0.005 M aq. hexanesulfonic acid/acetic acid (70/30/1,v/v). The liquid product was simply dissolved in acetonitrile/water/acetic acid (70/30/1,v/v) and filtered; the solid product was briefly ground, dissolved in the same solvent, and filtered. The precision (rsd) of the method for diphenhydramine in the liquid sample is 0.52%, and 0.50% for the solid sample. The method is linear up to 200 μg/mL. Based on spiking studies, the recoveries are 100.1% for the liquid sample, and 99.2% for the solid sample. The method was applied to the study of the thermal stability of the drug by following the degradation of diphenhydramine in the two products at temperatures in the 42°C to 62°C range for up to 16 weeks. Shelf lives of the products were determined assuming zero and first order kinetics of decomposition, and are at least 163 days for the liquid product, and at least 255 days for the solid product.